The development of transdermally deliverable pharmaceutical compositions typically involves a screening and refinement process in which a large number of pharmaceutical compositions are evaluated. Typically the compositions include one or more pharmaceuticals and one or more compounds (commonly known as excipients or enhancers) that increase diffusion of the pharmaceutical(s) across the membrane of interest (e.g., skin). Hundreds of useful excipients are known, and the specific choice of excipients for a given pharmaceutical typically involves an extensive screening process involving many membrane diffusion measurements.
Typical systems for measuring membrane diffusion have two chambers separated by a membrane (e.g., skin). Typically, one chamber contains a pharmaceutical composition to be tested (e.g., as a solution or in a transdermal patch), and the other chamber contains a recipient solution representative of serum. The pharmaceutical composition and the recipient solution each contact opposite surfaces of the membrane. The concentration of the pharmaceutical in the receiving solution is periodically measured and the diffusion rate of the pharmaceutical across the membrane determined. In order to obtain accurate membrane diffusion measurements, it is typically important that air gaps between the pharmaceutical composition, the receiving solution, and the membrane be avoided.
Widely used commercially available systems of the two-chamber type include Ussing chambers, Franz cells, in-line cells, and horizontal cells. Many such devices are only capable of making individual measurements and/or require relatively large areas of membrane to operate.
Systems that can perform multiple diffusion measurements in parallel using a single membrane have been reported. In essence, such systems divide the membrane into a plurality of separate regions, each of which serves as a membrane of a distinct two-chamber type cell. In such systems, it is generally important that the cells remain effectively isolated from each other (i.e., contents of one cell cannot enter into another cell).
There remains a need in the art for systems and methods that are useful for rapidly screening large numbers of formulations while efficiently using the membrane material.